A decade of molecular studies of fragile X syndrome

Annu Rev Neurosci. 2002;25:315-38. doi: 10.1146/annurev.neuro.25.112701.142909. Epub 2002 Mar 20.


Fragile X syndrome is one of the most common forms of inherited mental retardation. In most cases the disease is caused by the methylation-induced transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene that occurs as a result of the expansion of a CGG repeat in the gene's 5'UTR and leads to the loss of protein product fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that associates with translating polyribosomes as part of a large messenger ribonucleoprotein (mRNP) and modulates the translation of its RNA ligands. Pathological studies from the brains of patients and from Fmr1 knockout mice show abnormal dendritic spines implicating FMRP in synapse formation and function. Evidence from both in vitro and in vivo neuronal studies indicates that FMRP is located at the synapse and the loss of FMRP alters synaptic plasticity. As synaptic plasticity has been implicated in learning and memory, analysis of synapse abnormalities in patients and Fmr1 knockout mice should prove useful in studying the pathogenesis of fragile X syndrome and understanding learning and cognition in general. If an appreciable portion of the total variance (in IQ) is due to sex linked genes, it is of more importance that a boy should have a clever mother than a clever father. Hogben 1932 (quoted in Lehrke 1974)

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / abnormalities*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Differentiation / genetics*
  • Cognition Disorders / genetics
  • Cognition Disorders / metabolism
  • Cognition Disorders / physiopathology
  • Dendrites / metabolism
  • Dendrites / pathology*
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / metabolism
  • Fragile X Syndrome / physiopathology
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Mice
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity / genetics*
  • RNA-Binding Proteins*
  • Synapses / metabolism
  • Synapses / pathology


  • FMR1 protein, human
  • Fmr1 protein, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein